Cyclosporine, an immunosuppressant, attenuates phorbol-induced lung injury in rats.
OBJECTIVE
White cell activation in the lung plays a critical role to induce lung injury and lymphocytes in the thoracic duct system may also participate. We evaluated the effect of cyclosporine on phorbol myristate acetate (PMA)-induced lung injury.


METHODS
We used an in situ isolated, blood perfused rat lung model to measure pulmonary arterial pressure (PAP) and lung weight gain (LWG; g) for 50 minutes after a bolus injection of PMA (0.05 microg/mL). Oxygen radical release was estimated by an LKB 1251 luminometer and by nitric oxide (NO) release as measured by an ENO-20 NO analyzer.


RESULTS
In the group exposed to PMA alone, the mean PAP increased from 16.53 +/- 1.28 to 43.33 +/- 3.40 mm Hg (P < .001), and lung weight increased by 4.35 +/- 0.67 g during the 50-minute perfusion after PMA challenge (P < .001). In vitro measurement showed that PMA induced a significant increase in oxygen radical release (P < .001). PMA attenuated NO release (P < .001) into the perfusion system. Pretreatment with cyclosporine (3 mg/kg) for 3 days prevented the increases in both PAP (P < .01) and LWG (P < .001). NO release was maintained in cyclosporine-pretreated rats. Cyclosporine also showed dose-dependent attenuation of oxygen radical release by PMA-activated white blood cells.


CONCLUSIONS
The mechanisms responsible for the protective effect of cyclosporine on the lung injury induced by phorbol may be related to an attenuation of oxygen radical production with maintenance of NO release.
Su
C L
CL
School of Respiratory Therapy and Wangfang Hospital, Taipei Medical University, Taipei, Taiwan.
Chen
C F
CF
Chiang
L L
LL
Lee
C N
CN
Wang
D
D
Lo
S L
SL
Kao
S J
SJ
D055371:Acute Lung Injury / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D049449:Luminescence; D008168:Lung / Q000033:anatomy & histology; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate